The proposed project will use the guinea pig as a model for transplacental transmission of cytomegalovirus (CMV) and will study congenital CMV infection. The contribution that host immune responses provide in the control of GPCMV infection will be investigated. Specifically, the role that humoral and cell mediated immunity play in allowing the passage of virus across the placental barrier and in permitting the establishment of congenital infection will be evaluated by determining immune responses and virus pathogenesis during primary infection, reinfection and reactivation of infection in mothers and their offspring. Virus distribution, gross and histologic abnormalities and antibody responses will be examined. T cell functions will be assessed by lymphocyte stimulation, lymphocytoxicity and delayed hypersensitivity skin testing. Phagocytic, chemotactic and antiviral activities will be measured in macrophages and neutrophils. Results obtained on immune responses, virus distribution and pathology will be correlated. The role played by humoral and cell mediated immunity in the control of primary CMV infection, reinfection and in the frequency of recurrences during pregnancy will be elucidated. In addition, immune responses and viral pathogenesis will be sought in offspring; and the mechanisms by which virus persistence or recovery occur will be established. Clarification of these processes in guinea pigs will facilitate understanding of the mechanisms of human prenatal and perinatal CMV infections.